Investigative clinical chemotherapeutic studies in children with acute leukemia, malignant lymphoma, histiocytosis X, and malignant solid tumors (brain tumors, neuroblastoma, Wilms' tumor, osteogenic sarcoma, Ewing's sarcoma, soft tissue sarcoma, and miscellaneous malignant neoplasms) are conducted in three areas: (a) Phase I coordinated studies of human pharmacologic and toxicologic aspects of new anticancer agents and new combinations and dosage regimens; (b) Phase II systematic investigations of the effectiveness of individual anticancer agents or treatment programs in specific tumors; and (c) Phase III comparative evaluations of selected drugs or therapy regimens. The functioning cooperative group study mechanism is utilized to increase the size of the study population and to shorten the duration of the study. Independent investigative probes are undertaken to explore leads resulting from or directed toward group studies. Such activities include drug trials with new combinations or new dosage schedules, evaluation of treatment of CNS leukemia, exploratory immunologic studies, and investigation of techniques to improve supportive care. Several intergroup and national studies, ongoing and projected (National Wilms' Tumor Study, Intergroup Rhabdomyosarcoma Study, Intergroup Ewing's Sarcoma Study, Histiocytosis Study, Hodgkin's Disease Study) are included. Increasing activity will be directed toward the evaluation of multimodal therapy regimens in the management of childhood cancer in randomized clinical trials.